Ureases:  Quantum Chemical Calculations on Cluster Models

Suárez, Dimas; Díaz, Natalia; Merz, Kenneth M.

doi:10.1021/ja030145g

Cited by 89 publications

(127 citation statements)

References 34 publications

(61 reference statements)

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“…Studies showed that one of the nickel atoms bonded with the carbon atom of urea, while the other combined with the nitrogen. Similar results were presented by Andrich et al [25], who investigated the kinetics of urea degradation in a model wine solution using an acid urease and immobilized urease. The researchers determined that the reaction is a pseudo-first-order reaction.…”

Section: Enzymatic Decomposition Of Ureasupporting

confidence: 85%

Urea removal from aqueous solutions—a review

2016

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The abundance of urea in the natural environment is dictated by the fact that it is one of the major products of mammalian protein metabolism. Due to the extensive use of urea in many branches of industry, it is produced in large quantities. Urea enters into the environment not only with wastewater from the production plants but also by leaching from the fields, agro-breeding farms, and the effluents from the plants using it as a raw material. There are many methods of urea removal, but most of them are still being developed or are very new. The methods themselves differ in terms of physicochemical nature and technological ingenuity. Many wastewater treatment methods include processes such as hydrolysis, enzymatic hydrolysis, decomposition in the biological bed, decomposition by strong oxidants, adsorption, catalytic decomposition, and electrochemical oxidation. In this work, methods of urea removal from aqueous solutions have been reviewed. Particular attention was paid to electrochemical methods.

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Section: Enzymatic Decomposition Of Ureasupporting

confidence: 85%

Urea removal from aqueous solutions—a review

2016

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“…This last interaction has been found to determine the coordination mode of urea in QM calculations of cluster models of the urease active site. 46 Although not directly involved in urea coordination, contacts between HE2@His219, and HE2@His230 with OD2@Asp221 are readily identifiable. These residues form a His-Asp-His "triad" that remains stable over the entire MD simulation, with average inter-residue distances of 2.15Å.…”

Section: 2-structure Of the Active Sitementioning

confidence: 99%

Catalyzed Decomposition of Urea. Molecular Dynamics Simulations of the Binding of Urea to Urease

Estiú

Merz

2006

Biochemistry

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We present the results of molecular dynamics simulations on the urea/urease system. The starting structure was prepared from the 2.0Å crystal structure of Benini et al. of DAP-inhibited urease (PDB code 3UBP), 1 and the trimeric structure (2479 residues) resulted in 180K atoms after solvation by water. The force field parameters were derived using the bonded model approach described by Hoops et al. 2 Three different systems were analyzed, each one modeling a different protonation pattern for the His320 and His219 residues. In each case, the three monomers of urease have been analyzed separately. The time averaged structures observed in the three monomers suggest that urease could follow two different competitive mechanisms. A "protein assisted proton transfer" mechanism points to Asp221 as crucial for catalysis. An "Asp mediated proton transfer" involves the transfer of a proton from the bridging OH to a NH 2 moiety of urea, assisted by Asp360 in the active site. The impact of the simulation results on our understanding of urease catalysis are discussed in detail.The reliable prediction of the mechanism involved in the selectivity and efficiency of enzyme catalyzed reactions continues to challenge both experimental and computational researchers. 3-9 Mutagenic and biochemical procedures, as well as a variety of computational methodologies have been applied with the goal of understanding the enzymatic effect on reactivity, and several working hypotheses have been proposed. Among them, there is general agreement of the role played by the reduction of the free energy of activation, 3 but the origins of the free energy lowering, which involves non-covalent and covalent effects, is the subject of ongoing debate. 10 Non-covalent factors involve transition state electrostatic stabilization, 11 ground state destabilization and desolvation, 12 reduction of reorganization energy by binding in near attack conformations, 13 entropy trapping, 14 as well as several other related effects. Covalent and non-covalent effects are not exclusive, and rate enhancement can come from both effects, as well as from others. Covalent factors are dominant, whenever present. 15 They usually occur in metalloenzymes, where the metal centers covalently bind the substrate, stabilizing the transition state complex and leading to highly proficient catalysts. 10, 16 This is the case of the metalloenzyme urease, whose proficiency is presently a matter of extensive discussion, as values of 10 17 and 10 32 have been determined by experimental and theoretical means. 17, 18Urea amidohydrolase (urease) is a nickel-containing enzyme that catalyses the hydrolysis of urea to produce ammonia and carbon dioxide in the last step of nitrogen mineralization. 1, 19-25 The mechanism of the catalyzed reaction continues to be of interest, and there is still no agreement on whether the reaction involves a carbamic acid intermediate, a cyanate * To whom correspondence should be addressed. .edu † Present address: Department of Chemistry, Quantum Theory Project, ...

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“…[1][2][3][4] In contrast, when catalyzed by ureases, urea is generally believed to undergo hydrolysis rather than ammonia elimination. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] The products of hydrolytic decomposition have been reported to be either HCO 3 − and NH 4 + or ammonium carbamate depending on the buffer system. 19 These products are most readily rationalized to arise from an addition-elimination sequence.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][29][30][31] A B3LYP study on cluster models of the active site of ureases was carried out recently. 15 Models of various resting states of the active site were modeled and investigated, and mono-and bidentate modes of urea coordination were considered. Estiu and Merz 17 tested different mechanisms of urea decomposition in the gas phase and in solution modeled by the isodensity continuum polarizable model (ICPM).…”

Section: Introductionmentioning

confidence: 99%

Why Urea Eliminates Ammonia Rather than Hydrolyzes in Aqueous Solution

Alexandrova

Jorgensen

2007

J. Phys. Chem. B

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A joint QM/MM and ab initio study on the decomposition of urea in the gas phase and in aqueous solution is reported. Numerous possible mechanisms of intramolecular decomposition and hydrolysis have been explored; intramolecular NH 3 -elimination assisted by a water molecule is found to have the lowest activation energy. The solvent effects were elucidated using the TIP4P explicit water model with free energy perturbation (FEP) calculations in conjunction with QM/ MM Monte Carlo simulations. The explicit representation of the solvent was found to be essential for detailed resolution of the mechanism, identification of the rate-determining step, and evaluation of the barrier. The assisting water molecule acts as a hydrogen shuttle for the first step of the elimination reaction. The forming zwitterionic intermediate, H 3 NCONH, participates in 8-9 hydrogen bonds with water molecules. Its decomposition is found to be the rate-limiting step, and the overall free energy of activation for the decomposition of urea in water is computed to be ca. 37 kcal/mol; the barrier for hydrolysis by an addition/elimination mechanism is found to be ca. 40 kcal/mol. The differences in the electronic structure of the transition states of the NH 3 -elimination and hydrolysis were examined via natural bond order analysis. Destruction of urea's resonance stabilization during hydrolysis via an addition/elimination mechanism, and its preservation in the rearrangement to the H 3 NCONH intermediate were identified as important factors in determining the preferred reaction route.

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Ureases: Quantum Chemical Calculations on Cluster Models

Cited by 89 publications

References 34 publications

Urea removal from aqueous solutions—a review

Urea removal from aqueous solutions—a review

Catalyzed Decomposition of Urea. Molecular Dynamics Simulations of the Binding of Urea to Urease

Why Urea Eliminates Ammonia Rather than Hydrolyzes in Aqueous Solution

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